Race and sex differences in erythrocyte Na+, K+, and Na+-K+-adenosine triphosphatase.

Lasker, Norman; Hopp, Laszlo; Grossman, Susan D.; Bamforth, R; Aviv, Abraham

doi:10.1172/jci111894

Cited by 76 publications

(31 citation statements)

References 44 publications

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“…The assay method of EG Na + ,K + -ATPase in this investigation was different from that described in our previous work, 7 and it may account for the differences in the values of the activity of the enzyme between the two studies. However, the results of both investigations are in agreement.…”

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confidence: 67%

“…Blood pressure measurements and blood sampling were performed as described previously. 7 All subjects, including parents of the two adolescents, signed an informed consent approved by the Research Committee of the University of Medicine and Dentistry of New Jersey.…”

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confidence: 99%

“…Preparations of EGs for the Na + ,K + -ATPase assay and measurements of RBC Na + and K + concentrations were performed as previously described. 7 The Na + ,K + -ATPase assay in this work was based on the ouabain-sensitive hydrolysis of radiolabeled [-y- 32 P]adenosine 5'-triphosphate (ATP) and the chromatographic separation of adenosine 5'-diphosphate (ADP) and inorganic phosphate (P,) from ATP. In the previous work 7 the P, in the assay medium was measured using the Fiske and Subbarow method.…”

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Erythrocyte ghost Na+,K+-ATPase and blood pressure.

Rygielski

Reddi²,

Kuriyama

et al. 1987

Hypertension

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SUMMARY To examine the relationship between body mass index, blood pressure, and the Na + ,K + -adenosine triphosphatase (ATPase) system, we measured the erythrocyte ghost Na + ,K + -ATPase and the erythrocyte Na + concentration in 120 blacks and 127 whites (136 males and 111 females). Blacks showed a 13.9% higher erythrocyte Na + (7.63 ± 0.19 vs 6.70 ± 0.11 [SEM] mEq/L; p = 0.0001) and a 16.1% lower erythrocyte ghost Na + ,K + -ATPase activity (140.3 ± 4.2 vs 167.3 ± 4.7 nmol inorganic phosphate/mg protein/hr; p = 0.0002) than whites. Male subjects demonstrated a 6.4% higher erythrocyte Na + (7.35 ± 0.17 vs 6.91 ± 0.14 mEq/L; p= 0.043) and an 11.5% lower Na + ,K + -ATPase activity (145.7 ±3.7 vs 164.7 ± 5.5 nmol inorganic phosphate/mg protein/hr; p = 0.0015) than female subjects. Significant (p<0.001) negative correlations were identified for the systolic, diastolic, and mean blood pressure levels and the erythrocyte ghost Na + ,K + -ATPase. These findings were complemented by positive correlations for the blood pressure levels and erythrocyte Na + concentrations. The body mass index was negatively correlated with erythrocyte ghost Na + ,K + -ATPase and it accounted for 6.7%, 5.6%, and 6.1% of the variabilities in the systolic, diastolic, and mean blood pressure levels, respectively. Variabilities of 1.4% systolic, 12.3% diastolic, and 11.1% in mean arterial pressure were attributable to the erythrocyte ghost Na + ,K + -ATPase activity. Provided that findings in erythrocytes also reflect the relative status of the vascular smooth muscle cell Na + ,K + -ATPase, the predisposition of black, male, and obese persons to hypertension may relate, among other factors, to a lower activity of this enzyme system, which results in an increased vascular tone. Supported in part by grants-in-aid from the American Heart Association (84-765) and the American Heart Association New Jersey Affiliate (83-23) and a grant from the National Heart, Lung, and Blood Institute (R23HL29221). Dr. Kuriyama is a recipient of a research fellowship from the National Kidney Foundation of New York-New Jersey.Address for reprints: Abraham Aviv, M.D., Hypertension Research Unit, Room F-578 Medical Science Building, University of Medicine and Dentistry of New Jersey, 185 South Orange Avenue, Newark, NJ 07103.Received October 6, 1986; accepted April 22, 1987.(for a review see References 1-3) and obesity 4 " 6 of abnormalities in erythrocyte Na + and the Na + ,K + -ATPase system. Such studies have usually examined a relatively small number of subjects. Furthermore, by comparing hypertensive with normotensive or obese with nonobese subjects, these studies have treated the BMI and blood pressure level as discontinuous entities rather than as variables with continuous distributions. In the present report we describe the relationships among the erythrocyte ghost (EG) Na + ,K + -ATPase, RBC Na + , BMI, blood pressure, as well as other related parameters in a large group of men and women who participated in this investigation without being categorized a pr...

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confidence: 67%

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confidence: 99%

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confidence: 99%

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Erythrocyte ghost Na+,K+-ATPase and blood pressure.

Rygielski

Reddi²,

Kuriyama

et al. 1987

Hypertension

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“…Constitutional variations in erythrocyte Na/K ATPase activity have been associated with sex and ethnic origin, with lower activity having been reported in men than women, in blacks than whites, in Asians than Scandinavians [18,19], and in people of Semitic origin than Caucasians [14,15,20]. Semitic peoples are predisposed to severe and early diabetic neuropathy [9].…”

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confidence: 99%

“…Na/K ATPase activity in erythrocytes varies according to ethnic origin. It is lower in blacks and North Africans, who are predisposed to neuropathy in the case of diabetes [9], than in Caucasians and Scandinavians [18,19].…”

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Association of diabetic neuropathy with Na/K ATPase gene polymorphism

Vague¹,

Dufayet²,

Coste³

et al. 1997

Diabetologia

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Neuropathy is a leading cause of disability in diabetes mellitus. Unlike diabetic retinopathy which is an almost constant long-term complication, diabetic neuropathy occurs in only 50 % of cases [1]. This phenomenon is comparable to that observed with diabetic nephropathy [2] which has been associated with genetic susceptibility [3,4]. A number of facts suggest Diabetologia (1997) 40: 506-511 Association of diabetic neuropathy with Na/K ATPase gene polymorphism Summary Diabetes mellitus induces a decrease in Na/K ATpase activity in man and animals, and this decrease plays a role in the development of diabetic neuropathy. Na/K ATPase is encoded by various genes, of which the ATP1 A1 gene is expressed predominantly in peripheral nerves and in erythrocytes. To investigate whether a polymorphism in the Na/K ATPase genes could explain the predisposition of some patients with insulin-dependent diabetes mellitus (IDDM) to develop polyneuropathy, a restriction fragment length polymorphism (RFLP) of the ATP1 A1 gene was studied together with erythrocyte Na/K ATPase activity in 81 Caucasian patients with more than 10 years' duration of IDDM. Associations with diabetic neuropathy, retinopathy and nephropathy were sought. Digestion of the first intron of the ATP1 A1 gene by the Bgl II restriction enzyme revealed a dimorphic allelism. Frequency of the restricted allele was 0.18 in this selected series (however, it was 0.10 in representative samples of IDDM patients and of normal subjects in our area). Mean erythrocyte Na/K ATPase activity was lower in diabetic patients than in 42 control subjects (292 ± 10, vs 402 ± 13 nmol Pi ⋅ mg protein − 1 ⋅ h − 1 , p < 0.0001) and was not related to HbA 1c value or to diabetes duration. It was lower in the group of the 28 patients bearing the restricted allele (241 ± 10 vs 319 ± 11 nmol Pi ⋅ mg protein − 1 ⋅ h − 1 , p < 0.0001).Neuropathy was absent in 50 patients, mild in 15 and severe in 16. When classified accordingly the three groups of patients did not differ with respect to sex, age and duration of diabetes. The respective frequency of the restricted allele among the groups was 10, 73 and 81 %, (p < 0.0001) and mean erythrocyte Na/K ATPase activity was respectively: 322 ± 10.7 nmol Pi ⋅ mg protein − 1 ⋅ h − 1 , 268 ± 15 and 229 ± 17, (p < 0.001). A borderline association between renal status or retinal status and repartition of polymorphism and a borderline correlation between renal status and Na/K ATPase activity were found, but significance disappeared after checking for the presence or absence of neuropathy. IDDM patients bearing the ATP1 A1 variant detected by Bgl II RFLP are much more frequently affected by neuropathy (relative risk 6.5, with 95 % CI 3.3-13). Identification of this risk factor may help to prevent this complication. It is suggested that the restricted allele is in linkage disequilibrium with a genomic mutation allowing diabetes to induce a greater impairment of Na/K ATPase activity which could in turn favour the development of neuropathy. [Diabetologia (199...

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